Chemistry of Heterocyclic Compounds PDF

HETEROCYCLIC COMPOUNDS ====================== ### METHODS OF PREPARATION AND CHEMICAL REACTIONS OF HETEROCYCLIC COMPOUNDS #### METHODS OF PREPARATION OF PYRROLE: i. **From bone oil:** Bone oil is rich of pyrrole. The basic and acidic impurities of Bone oil are removed by sequential treatment...

HETEROCYCLIC COMPOUNDS ====================== ### METHODS OF PREPARATION AND CHEMICAL REACTIONS OF HETEROCYCLIC COMPOUNDS #### METHODS OF PREPARATION OF PYRROLE: i. **From bone oil:** Bone oil is rich of pyrrole. The basic and acidic impurities of Bone oil are removed by sequential treatment of it with dilute acidic and dilute basic solutions. The treated Bone oil is then subjected for fractional distillation, the fraction obtained between 373K and 423K is collected. The collected fraction is then purified with KOH to obtained potassiopyrrole. Steam distillation of potassiopyrrole gives pure pyrrole. C H NH ii. **From succinimide:** Succinimide when is distilled with Zn dust it reduces the succinimide to pyrrole. Zn dust O iii. **From Furan:** Industrially pyrrole is prepared by passing a mixture of furan and ammonia over alumina over 400° C. iv. **Pall-Knorr synthesis:** In this method, when a 1,4-diketone is heated with ammonia or a primary amine it gives the corresponding pyrrole derivatives. O H #### PROPERTIES OF PYRROLE: v. **Physical Properties of pyrrole:** Pyrrole is a colorless liquid with boiling point 131° C. It is highly sensitive to air, when pyrrole is exposed to air it turns brown and gradually resinifies. Pyrrole is slightly soluble in water but completely miscible in ether and ethanol. vi. **Chemical Properties:** Pyrrole is an aromatic compound and more reactive than benzene. Because of the aromatic nature pyrrole gives all characteristic reactions (electrophilic substitution reactions) of aromatic compounds such as halogenation, nitration, sulphonation, Friedel-Crafts reactions etc. E+ a. **Electrophilic Substitution Reactions of Pyrrole:** Pyrrole undergoes electrophilic substitution reactions at position C-2. i. **Halogenation:** Pyrrole reacts with halogens \[X2 (X2 = Cl2, Br2 and I2)\] to give tetrahalopyrrole. For example, Reaction of bromine with pyrrole gives tetrabromopyrrole. \+ Br~2~ Br Br Pyrrole 2,3,4,5-tetrabromopyrrole ii. **Nitration:** Nitration of pyrrole is achieved by reacting it with HNO3 in acetic anhydride. The reaction of HNO3 and acetic anhydride resulted acetyl nitrate in which O O O iii. **Sulphonation:** Sulphonation of pyrrole is achieved by reacting it with sulfur trioxide (SO3) -- pyridine mixture in ethylene chloride. \+ SO3 N. SO3H Pyrrole iv. **Friedel-Crafts Acylation:** Reaction of pyrrole with acetic anhydride under heating condition gives 2-acetylpyrrole. \+ CH~3~-C-O-C-CH~3~ v. **Diazotization:** Pyrrole reacts with benzenediazonium chloride in acidic medium to give 2-phenylazopyrrole. vi. **Reimer-Tiemann Reaction:** Pyrrole reacts with Chloroform in presence of KOH to give 2-Formylpyrrole. This reaction is known as Reimer-Tiemann reaction. It also takes place through electrophilic substitution reaction mechanism. \+ CH3Cl Pyrrole b. **Reduction:** Pyrrole can be reduced to pyrrolidine (tetrahydropyrrole) by H2 gas in Raney Ni at very high temperature (473K). c. **Oxidation:** Pyrrole when oxidized with Chromium trioxide in H2SO4, it gives Malecimide. Pyrrole #### METHODS OF PREPARATION OF FURAN: vii. **From Mucic acid:** Dry distillation of mucic acid first gives Furoic acid which on decarboxylation by heating gives Furan. - CO~2~ - H~2~O viii. **From Furfural:** Furan is synthesized from furfural which is obtained by acid-hydrolysis of pentose sugars. - 3H2O O CHO - CO O ix. **Paal-Knorr Synthesis:** Dehydration of 1,4-diketone with P2O5 (phosphorous Pentaoxide) gives derivatives of Furan. 3. #### PROPERTIES OF FURAN: x. **Physical Properties of Furan:** Furan is colorless liquid. Its boiling point is 31.4° C. It has an odor similar to Chloroform. It is insoluble in ether but soluble in most of the organic solvents. xi. **Chemical Properties of Furan:** furan is an aromatic compound and more reactive than benzene. Because of the aromatic nature, furan gives all characteristic reactions (electrophilic substitution reactions) of aromatic compounds such as halogenation, nitration, sulphonation, Friedel-Crafts reactions etc. H [4 3] 5 2 O a. **Electrophilic Substitution Reactions of Furan:** Furan undergoes electrophilic substitution reactions at position C-2. i. **Halogenation:** Furan reacts with halogens \[X2 (X2 = Cl2, Br2 and I2)\] to give 2- halofuran. For example, reaction of bromine with Furan gives 2-bromofuran. O ii. **Nitration:** Nitration of furan is achieved by reacting it with HNO3 in acetic anhydride. The reaction of HNO3 and acetic anhydride resulted acetyl nitrate in which O O O iii. **Sulphonation:** Sulphonation of Furan is achieved by reacting it with sulfur trioxide (SO3) -- pyridine mixture in ethylene chloride at 100° C. O. SO3H iv. **Friedel-Crafts Acylation:** Reaction of furan with acetic anhydride in presence of BF3 gives 2-acetylfuran. b. **Reduction:** On catalytic hydrogenation of furan, the tetrehydrofuran (THF) is obtained. THF is used as a solvent in place of ether in the Grignard reactions. c. **Gattermann Koch Synthesis:** When furan is treated with a mixture of HCN and HCl in the presence of Lewis acid catalyst AlCl3, furfural is obtained as final product. d. **Diels-Elder Reaction:** Furan is the only heterocyclic compound which undergoes Diels-Elder reaction. Diels-Elder reaction is a cycloaddtion reaction of 4π-system to 2π- system. #### METHODS OF PREPARATION OF THIOPHENE: xii. **From *n*-Butane:** Thiophene is obtained when n-butane is heated with elemental sulphur at very high temperature (923K). H2C xiii. **Laboratory Method:** When sodium succinate is heated with phosphorous sulphide, thiophene is obtained. xiv. **Industrial Method:** Industrially, thiophene is prepared by passing a mixture of acetylene and hydrogen sulphide through a tube containing alumina (Al2O3) at 673K. xv. **Pall-Knorr synthesis of thiophene derivatives:** In this method, dehydration of 1,4- diketone with P2S5 (phosphorous Pentasulphide) gives derivatives of thiophene. #### PROPERTIES OF THIOPHENE: xvi. **Physical Properties of thiophene:** Thiophene is colorless liquid. Boiling point of thiophene is 357 K. It smells like benzene. It is soluble in alcohol and ether but insoluble in water. xvii. **Chemical Properties of thiophene:** Thiophene is an aromatic compound and more reactive than benzene. Because of the aromatic nature, thiophene gives all characteristic reactions (electrophilic substitution reactions) of aromatic compounds such as halogenation, nitration, sulphonation, Friedel-Crafts reactions etc. H [4 3] 5 2 S a. **Electrophilic Substitution Reactions of Thiophene:** Thiophene undergoes electrophilic substitution reactions at position C-2. i. **Halogenation:** Thiophene reacts with halogens \[X2 (X2 = Cl2, Br2 and I2)\] to give 2- halofuran. For example, reaction of bromine with Thiophene in absence of any halogen carrier gives 2,5-dibromothiophene. Thiophene 2,5-dibromothiophene I S ii. **Nitration:** 2-Nitrothiophene is obtained when nitration of thiophene is performed by reacting it with fuming HNO3 in acetic anhydride. The reaction of HNO3 and acetic anhydride resulted acetyl nitrate in which --NO2 acts as an electrophile. O O O S NO2 iii. **Sulphonation:** Sulphonation of thiophene is achieved by reacting it with cold concentrated H2SO4. Thiophene-2-sulphonic acid is obtained as product. Thiophene Thiophene-2-sulfonic acid iv. **Friedel-Crafts Acylation:** Reaction of thiophene with acetic anhydride in presence b. **Reduction:** On catalytic hydrogenation of thiophene, the tetrehydrothiophene (Thiophane) is obtained. ### COMPARISON OF BASICITY OF PYRROLE, PYRIDINE AND PIPERIDINE \<